A Novel Prognostic Model for Gastric Cancer with EP_Dis-Based Co-Expression Network Analysis

Round 1

Reviewer 1 Report

My comments on the manuscript:

1) These methods are considered novel as this research employed the classical WGCNA that uses Pearson's Correlation Coefficients (PCC) and improvised coding utilising the combined EP_dis that uses Euclidean distance and PCC for the network construction. How can other researchers apply this novel method?

2) PCC measures the strength and direction of the linear relationship between two variables whereas, Euclidean distance quantifies the overall dissimilarity between two data points based on the absolute differences between their feature values.

3) Combining Euclidean distance and Pearson correlation coefficient can capture both the dissimilarity between samples and the similarity in gene expression patterns. This approach allows for a more comprehensive analysis of co-expression relationships in gene expression data and can provide insights into the underlying biological processes.

4) Application of statistical methods such as cox regression analysis and TimeROC analysis in this research enhance the robustness and reliability of the findings though it requires experimental validation. It also minimises the risk of false positives.

5) Make sure all tables and figures including the supplementary files are described in the manuscript.

6) What are the criteria used in selecting the RNAseq data? It should be explained in Line no 79.

7) Line no 85. Change to Illumina platform

8) Most Figures are not clear. E.g., Figure 1 - 5. 

9) Line 259. How do you define the immunohistochemical images in Figure 5 as significantly differentially expressed? Each figure should be labelled.

10) Line 279-284. Not suitable to discuss the methodology in the discussion.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

In its present state, I do not recommend accepting this paper. “Unfortunately, the literature reviewed in the introduction is inadequate. The manuscript lacks a convincing theoretical framework, doesn’t depict systematic study plan, moreover, the results haven’t been discussed clearly and the conclusion hasn’t been inferred well. Some comments:

1.      What does EP_dis-based mentioned in the title means? EP_dis-based hasn’t been mentioned anywhere in the manuscript.

2.      Figure 1, 2, 3 and 4 lacks clarity and needs to have improved resolution.

3.      The significantly co-expressed gene pairs and their relevance hasn’t been clearly discussed.

4.      Numerous typographical errors exist like for instance Pg 2, line 85 (Illumina platform).

5.      References 14 and 15 haven’t been cited in the main text.

6.      Pathway and network analysis (protein and gene level) should have been discussed.

Needs improvement by a native English speaker or a language editing service.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

1. For this statement "Gastric Cancer (GC) is a prevalent and deadly malignancy worldwide, ranking fifth 31 in incidence and fourth in mortality in 2020 [1]." the author should provide the latest statistics on 2022/2023 if possible. 

2. Unlike apoptosis, cell 42 necrosis, and autophagy, ferroptosis has distinct features and mechanisms [7]. Please provide some details on the distinct features and mechanisms. 

3. In the methods sections, the author should explain what is the statistical analysis they used to conduct the statistical analysis

4.  The author should provide the p values (P<0.05 or P>0.05) in the text of the results whenever they mention there is or there is no statistical significance 

5. Some Figurer are not clear. Please improve if possible. 

6. In the conclusion section please provide suggestions for future studies based on current findings.

 

Overall good

Author Response

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Author Response File: Author Response.pdf

Reviewer 4 Report

The manuscript has interesting work regarding A Novel Prognostic Model for Gastric Cancer with EP_dis-Based Co-expression Network Analysis and it would be a very good contribution to the applied sciences. 

However, few changes are required which are;

1. List of abbreviation should be added.

2. Results should be more elaborative.

3. Connect discussion contents with latest references. 

Minor editing of English language required

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

I have gone through the manuscript and the author's response. Manuscript looks much better now and can be accepted.

Minor improvements needed.